A Double‐blind,Randomized, Prospective Study of Epidural Steroid Injection vs. The mild® Procedure in Patients with Symptomatic Lumbar Spinal Stenosis

Background: Epidural steroid injections (ESIs) are commonly used to treat low back pain, including symptomatic lumbar spinal stenosis (LSS). Reports on LSS treatment with ESIs have not differentiated between neurogenic claudication, which is believed to result from nerve root compression, and lumbar radicular pain, thought to be caused by inflammation. While there is overlap between these groups, the clinical relevance of ESI treatment cannot be generalized between these 2 distinct diseases with completely different pathophysiological causes. Methods: This was a double‐blind, randomized, prospective study of ESI vs. the mild procedure in patients with symptomatic LSS, conducted at a single pain management center. Patient reported outcome measures included Visual Analog Scale, Oswestry Disability Index, and Zurich Claudication Questionnaire (ZCQ) patient satisfaction. Results: Thirty‐eight patients were randomized into 2 treatment groups, 21 in mild and 17 in ESI. At 6‐ and 12‐week follow‐up, patients treated with mild reported significantly greater pain decrease over time (P < 0.0001), and significantly greater functional mobility improvement over time (P < 0.0018) than ESI patients. At week 6, mild ZCQ patient satisfaction score of 2.2 indicated a higher level of satisfaction than for ESI with a score of 2.8. In addition, 12‐week ZCQ satisfaction score was 1.8, demonstrating sustained near‐term satisfaction in the mild group. No major mild or ESI device or procedure‐related complications were reported. Conclusions: This study demonstrated that in LSS patients suffering with neurogenic claudication, mild provides statistically significantly better pain reduction and improved functional mobility vs. treatment with ESI.     

Progesterone modulates m TOR in the hippocampus of mice after traumatic brain injury

the mechanistic target of rapamycin(m tor) is an intracellular protein kinase that functions as an energy and nutrient sensor in the cellular microenvironment of neurons. modulation of m tor is vital when nutrient and energy sources become limited. hypoxia, traumatic brain injury, cellular energy states, and growth factors all regulate the phosphorylation and total levels of m tor in cells. alterations in the microenvironment induce transduction of signals to downstream proteins by m tor allowing for cells to make the necessary adjustments to counteract stressors and survive. progesterone, a hydrophobic steroid hormone, has been shown in studies of non-neural tissue to be a suppressor of m tor and modulator of m tor phosphorylation. our study tested the effects of progesterone on m tor expression following traumatic brain injury. c57 bl/6 mice were treated with progesterone(8 mg/kg) at 1(intraperitoneal), 6(subcutaneous), 24(subcutaneous), and 48(subcutaneous) hours post closed skull traumatic brain injury. the hippocampus was then harvested 72 hours post injury and prepared for western blot analysis. we found that progesterone significantly decreased total m tor levels in all groups compared to sham treated with vehicle. this was further confirmed by immunostaining showing decreased cytoplasmic m tor levels compared to sham. our study shows progesterone is a significant modulator of m tor levels in the hippocampus of mice following traumatic brain injury.     

Description of physical activity in outpatients with schizophrenia spectrum disorders

This study describes physical activity level in outpatients with schizophrenia spectrum disorders (SSD) using extended‐wear pedometers. Demographic data, body fat and body mass index (BMI) measures were obtained from 24 outpatients. Participants were provided extended‐wear pedometers and instructed to wear them during waking hours for 1 week. More than 79% of subjects met Centres for Disease Control (CDC) obesity criteria. Participants wore pedometers, on average, 6 days during the week. Men walked more steps, walked longer distances, and burned more calories each day; differences were statistically significant for steps and distance on days 3 (t = 2.12, P = 0.045) and 5 (t = 2.19, P = 0.04). Higher percent body fat and BMI were significantly associated with fewer steps walked on most days. Extended‐wear pedometers are an easy‐to‐use, cost‐effective way to document physical activity and evaluate efforts to help this vulnerable group achieve activity‐related health improvements.     

Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform

The Gyrolab? xP is a microfluidic platform for conducting ligand binding assays (LBAs) and is recognized for its utility in discovery bioanalysis. However, few reports have focused on the technology for regulated bioanalysis. This technology has the advantage of low reagent consumption, low sample volume, and automated ligand binding methods. To improve bioanalysis testing timelines and increase the speed at which biotherapeutics are delivered to patients, we evaluated the technology for its potential to deliver high-quality data at reduced testing timelines for regulated bioanalysis. Six LBA methods were validated to support bioanalysis for GLP toxicokinetic or clinical pharmacokinetic studies. Validation, sample analysis, and method transfer are described. In total, approximately 4000 samples have been tested for regulated bioanalysis to support 6 GLP toxicology studies and approximately 1000 samples to support 2 clinical studies. Gyrolab? xP had high run pass rates (≥83%) and high incurred sample reanalysis (ISR) pass rates (>94%). The maximum total error observed across all QC levels for a given assay was <30% for all six LBAs. High instrument response precision (CV ≤5%) was observed across compact discs (CDs), and methods were validated to use a single standard curve across multiple CDs within a Gyrolab? xP run. Reduced bioanalysis timelines were achieved compared to standard manual plate-based methods, and methods were successfully transferred across testing labs, paving the way for this platform for use in late-stage clinical development.     

Heart Failure Management in Nursing Homes: A Scoping Literature Review

Heart failure (HF) affects 20% of nursing home (NH) residents, causing high morbidity and mortality. The optimal approach to HF management in NHs remains elusive. We conducted a scoping review of published guidelines and HF management interventions in NHs. A search for English publications since 1990 was conducted using PubMed, EMBASE, CINAHL, and Scopus, for scientific statements, guidelines, recommendations, or intervention studies that addressed at least 1 principle of HF management. Of 2545 records retrieved, 19 articles were retained after screening, and 2 additional articles identified through reference list manual searches. Six articles represented 5 guidelines and 15 described interventions. All guidelines endorsed the applicability of general HF guidelines to NH residents, tailored to comorbidities, frailty, and advance care preferences. Four addressed quality assurance but not feasibility and sustainability. Methodological quality of the interventions was poor, although results suggest that guideline-based HF management in NHs can improve nursing staff knowledge and job satisfaction, prescribing, and reduce acute care utilization. Clinically-based education for staff, and access to specialist mentorship are important. NH physician involvement was limited, and resident/family education potentially ineffective. Concerns about feasibility, sustainability, and quality assurance were identified in most interventions, and advance care planning was rarely addressed. HF guidelines for NH support the applicability of general HF guidelines to the care of NH residents, and published interventions suggest that guideline-based HF management in NHs is effective. Future work should support greater physician and resident engagement, advance care planning, and provide robust guidelines on developing feasible and sustainable interventions.